Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons
(2023) In Stem Cell Reports 18(8). p.1643-1656- Abstract
Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical... (More)
Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.
(Less)
- author
- organization
-
- Neurology, Lund
- Stem Cells & Restorative Neurology (research group)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Stem Cell Center
- MultiPark: Multidisciplinary research focused on ParkinsonĀ“s disease
- Regenerative Neurophysiology (research group)
- Division of Molecular Hematology (DMH)
- WCMM-Wallenberg Centre for Molecular Medicine
- Neural stem cell biology and therapy (research group)
- publishing date
- 2023-08
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cell therapy, Demyelination, Human brain, iPS cells, Myelin, Oligodendrocyte, Oligodendrogenesis, Remyelination, Stroke
- in
- Stem Cell Reports
- volume
- 18
- issue
- 8
- pages
- 14 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:85164805895
- pmid:37236198
- ISSN
- 2213-6711
- DOI
- 10.1016/j.stemcr.2023.04.010
- language
- English
- LU publication?
- yes
- id
- 99df6f61-6130-4c92-b4b1-7ae2ffb36869
- date added to LUP
- 2023-10-06 13:04:44
- date last changed
- 2024-10-18 20:57:11
@article{99df6f61-6130-4c92-b4b1-7ae2ffb36869, abstract = {{<p>Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.</p>}}, author = {{Martinez-Curiel, Raquel and Jansson, Linda and Tsupykov, Oleg and Avaliani, Natalia and Aretio-Medina, Constanza and Hidalgo, Isabel and Monni, Emanuela and Bengzon, Johan and Skibo, Galyna and Lindvall, Olle and Kokaia, Zaal and Palma-Tortosa, Sara}}, issn = {{2213-6711}}, keywords = {{Cell therapy; Demyelination; Human brain; iPS cells; Myelin; Oligodendrocyte; Oligodendrogenesis; Remyelination; Stroke}}, language = {{eng}}, number = {{8}}, pages = {{1643--1656}}, publisher = {{Cell Press}}, series = {{Stem Cell Reports}}, title = {{Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons}}, url = {{http://dx.doi.org/10.1016/j.stemcr.2023.04.010}}, doi = {{10.1016/j.stemcr.2023.04.010}}, volume = {{18}}, year = {{2023}}, }